starlight

still not done a mp. test as have been abroad. however, on return took some of the bromoketone and attempted to produce the aminopropanone.

tried first with NH3 and just got a load of pyrazine.

then did the delepine with the bromoketone in chloroform, filtered of the uronium salt, which was refluxed in ethanolic HCL. Ethanol was then evaporated. Ended up with some off-white powder which was washed with acetone till clean and white.

hurt the nose, but not nearly as irritating as the methylamino product.

120mg had no effects upon insufflation.

maybe we are dealing with the wrong positional isomer.

what's wierd though is that all other reactions of indane like the acylation above, and the formlyation with dichlorodimethylether seem to attach mainly at the 5 position. Why would I have the wrong isomer?

I will progress the mp. tests.

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Rhodium

The chloromethylation of indane produces a mixture of the 4- and 5-chloromethyl-indanes for example, and many other acylations/alkylations do too, with varying ratios between the two isomers (the ratio depending on a lot of factors).

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psychokitty

In order to reduce the carbonyl function to the methylene group directly, I would either use Li in liquid ammonia or a combination of the cathinone salt, ammonium formate, and Pd/C catalyst in water, heated to reflux until the gas evolution ceases. This suggested reduction is basically patterned after the one wherein O-acetyl-ephedrine is reduced to methamphetamine. This variation of the ammonium formate-Pd/C CTH reduction could include the use of those Pd BBs found in automotive catalytic converters. One could just add the Pd BBs to the aqueous mixture of the cathinone/ammonium formate-Pd/C and reflux. Since the roiling boil of the mixture should be enough to keep the reaction in motion, stirring wouldn't be needed and the continued evolution of gasses could serve as an effective visual aide to the progress of the reaction. Just a thought.

There are other alternative reducing agents. Published in the literature is sodium borohydride's use in the methcathinone reduction to ephedrine. I can post the experimental details if you're interested. The HI reaction is likely the best one for reducing the indanyl ephedrine to the indanyl amphetamine. HI has already been used to demethylate methoxy substituted amphetamines into their hydroxy ring-substituted counterparts safely. Since the structure of such molecules is able to survive the rigorous conditions of the demethylation reaction and since the HI easily reduces ephedrine to methamphetamine, HI should work well at reducing indanyl ephedrine to indanyl amphetamine (I guess they should correctly be referred to as "trimethylene" ephedrine and amphetamine derivatives but I'm going to continue using the indanyl prefix just because it looks better).

As for the application of the Delepine reaction in the synthesis of the indanyl cathinone derivative, from what I've read, it will not work. Apparently, the reaction of hexamine and a-haloacetophenones goes to completion with the formation of the intermediate complex which can then be hydrolyzed in ethanolic HCl to yield the desired a-aminoacetophenone derivative. However, according to an abstract (C.A.) that I have in my files, the Delepine reaction is not applicable to a-bromopropiophenone, which reacts with hexamine to form a complex that upon attempted hydrolysis, does not yield the expected a-aminopropiophenone. Hexamine may react with substituted a-bromopropiophenones to form the desired complex in question. I don't know. But the available literature seems to suggest otherwise. However, the Gabriel synthesis has successfully been applied to the a-aminopropiophenone synthesis utilizing the hydrazine hydrate hydrolysis of the complex formed from the reaction of a-bromopropiophenone and potassium phthalimide. I'll soon post the experimental details to this reaction as well.